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CHAPTER 4 Genetics 49

POSITIONAL OR MODIFIER TABLE 4-2 Transferases and Their Corresponding

EFFECTS OF GENES Sugars Added by the ABH Genes

Sometimes genes can interact with each other depend- ABH Gene Transferase Sugar
ing on their location on the chromosome pair. When
two genes are located on the same chromosome, they H L-fucosyltransferase L-fucose

are said to be in cis position. If the genes are located on A N-acetylgalactosamine N-acetylgalactosamine
homologous chromosomes (paired), they are said to transferase
be in trans position. For example, C and D are genes in
the Rh system. It has been found that C exerts an effect B Galactosaminyltransferase D-galactose

on D in the cis and trans states, which results in a

weakened expression of D. Some genes can modify or
suppress the expression of other genes, although in
the transferases are known as glycosyltransferases.
most cases the exact mechanism for this action is not
These have the specific job of adding sugars to basic
understood. Genes that are known to modify or sup-
precursor substances, resulting in the expression
press include In(Lu), which suppresses the expression
of carbohydrate-based blood group antigens. There-
of Lutheran genes, and Xºr, which suppresses the con-
fore, the carbohydrate blood group differs according
version of Rh precursor into detectable Rh traits.
to the sugars added to the precursor substances.
Table 4-2 lists the transferases for which the ABO
GENE ACTION genes code. A brief discussion of the basic biochem-
istry of the blood group systems is found in the chap-
Genetic information is found in the double strands of ters dealing with each system.
DNA. The sequence of base pairs that make up the DNA
determines the particular protein that is produced.
The base pairs are arranged in codons, each composed SILENT GENES
of three base pairs. Sixty-four codons have been iden-
tified. Most of these codons code for 1 of the 21 amino In some blood group systems, as stated previously,
acids; some are known as terminator codons and certain genes are considered silent because they do
signal that the protein synthesis is complete. not produce a detectable product. Such silent alleles
The DNA, through a process called transcrip- are known as amorphs. Table 4-3 gives a list of some
tion, assembles a protein known as messenger RNA of the silent genes of interest to blood bankers and
(mRNA), which carries a code for the production the phenotypes they produce when inherited in the
of the protein to be made within a cell. RNA is simi- homozygous state.
lar to a single strand of DNA. Ribose, however, re- Sometimes genes are considered silent because
places deoxyribose, and uracil is the base instead of another gene (suppressor gene) is inhibiting the
thymine. An enzyme, RNA polymerase, allows the expression of their products. An example of this is
DNA double strands to separate. The mRNA is
formed using one of the DNA strands as a template.
The process is somewhat complicated, and the
reader is referred to genetic texts for a complete TABLE 4-3 Silent Genes
explanation.
Once the mRNA is formed, it moves to the cell’s cy- Blood Group Blood Group Homozygous
toplasm, where it attaches to ribosomal RNA (rRNA). Gene System Phenotype
The rRNA reads the mRNA and attaches a third type of h ABO On or Bombay
RNA known as transfer RNA (tRNA). Each tRNA is
composed of three base pairs. This attachment contin-  Rh Rhnull
ues until a termination code is encountered. This pro- r
cess is known as translation and results in the
production of detectable proteins that differ according K0 Kell Kellnull or K0
to the sequence of amino acids forming them. This is Lu Lutheran Lu(a b)
how protein blood group traits differ. However, not all
blood group traits are protein in nature; some are Jk Kidd Jk(a b)
carbohydrate. In these cases, blood group genes work Fy Duffy Fy(ab)
to produce enzymes called transferases. Specifically,
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50 UNIT 2 Genetic and Immunologic Principles
found in the Lutheran blood group system. People who
inherit the In(Lu) gene in the homozygous state fail to
express the products of Lutheran genes they may have
inherited because of the inhibitory effect of In(Lu).
BLOOD GROUP NOMENCLATURE
Some attempts have been made to standardize blood
group nomenclature, but these attempts have not been
completely successful. For example, in typical
Mendelian genetics, dominant genes are usually capi-
talized, and recessive genes are lowercase. In blood
group genetics, expression is not standardized. In the
ABO system, for example, a person who is group A and
inherits an A gene from one parent and an O gene from
the other is genotypically noted as AO. Both A and O are
capitalized, even though A is considered dominant to O.
In the Rh system, a person who is heterozygous at the
Cc locus is genotypically noted as Cc. Although the c is
lowercase, it is not recessive to C but rather codominant
with it. Many methods are used to denote various blood
group genotypes and phenotypes. These are discussed
in detail in a 1990 review article by Issit and Crookston.3
Some blood group genes are denoted by single
letters such as M, K, and I. The phenotype resulting
from these genes can be written using a plus symbol
() to indicate the presence of the trait (detected by
using antibody directed toward the trait) or a minus
symbol () to indicate its absence. For example, RBCs
reacting with anti-M, anti-K, and anti-k but not with
anti-N would be phenotypically MNKk. This
designation is not used in the ABO system, however,
because RBCs reacting with anti-A but not with anti-B
are designated group A, not AB.
Sometimes the genes of a blood group system are
denoted by two letters with different superscripts to
differentiate the alleles. Genes of the Duffy system fall
into this category. The letters “Fy” indicate the Duffy
system, and a superscript “a” or “b” is placed with the
Fy to indicate alleles. Phenotypes in this system are
written using the same symbols in a format that
uses pluses and minuses to indicate the presence or
absence of traits. RBCs that react with Fya and not
with Fyb are phenotypically Fy(ab). This mode of
nomenclature is used in the Lutheran, Kidd, Scianna,
and Gerbich systems as well.
Numeric nomenclature has been developed for
most blood group systems. In this instance, each
gene is written with a letter and a number (e.g., the
Kell trait is K1). Phenotypes are written using a let-
ter followed by a colon and a positive number if the
particular trait represented by the number is present
or a negative number if the trait represented by the
number is absent (i.e., K: 1 would be written for
50
RBCs failing to react with antibody to K1). Genes are
written using the letter and a superscript number
(K1); K1 is the product of K1.
The Rh system is even more confusing for the stu-
dent of blood group systems because several different
nomenclatures are used. Chapter 10 discusses the
nomenclature used in this system in detail.
PUBLIC AND PRIVATE GENES
Certain genes and their resulting traits are found in
most of the population. These genes are referred to
as public genes. Other genes are exceedingly rare
and are sometimes referred to as private genes.
These can be found in few people, often only in a
particular race or family.
BLOOD GROUP GENES AS
GENETIC MARKERS
Because blood group genes are polymorphic, they
can be useful in detecting several types of genetic
problems. Disputed parentage is perhaps the most
common problem. Box 4-1 lists some of the blood
group systems that are commonly used in parentage
testing. The histocompatibility or human leukocyte
antigen (HLA) system and RBC enzyme studies, in
addition to detection of the product of red cell genes,
are useful in such testing.
By using blood group genetics, it is possible to ex-
clude people from parentage. Such exclusions are either
direct or indirect. In a direct exclusion, the offspring
possesses a trait that neither the mother nor the alleged
father possess, as in the following example:
Mother AA
Father OO
Child AB
BOX 4-1
Blood Group Systems Commonly Used
in Paternity Testing
ABO
Duffy
HLA
Kell
Kidd
MNSs
Rh
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CHAPTER 4 Genetics 51

The alleged father is directly excluded on the SUMMARY

basis that the child possesses a group B gene that he or
she could not have received from the mother or the
alleged father. The gene, therefore, must have been
contributed by another person.
Indirect exclusion refers to a case in which an off-
spring does not possess a gene that should have been
inherited. In the case shown below, the child should
possess the c gene because the alleged father is ho-
mozygous and should pass c to any of his offsprings.
The child, however, does not possess this gene; there-
fore, an indirect exclusion is established.
Mother CC
Alleged father cc
Child CC
Blood group genetics is extremely important to the
entire field of genetics. The study of inheritance in
the blood group systems has added to our knowledge
and understanding of how traits are inherited.
For the student of blood banking, a basic under-
standing of genetics is crucial. An understanding of
the production of detectable blood group traits and
the interaction of genes in relation to those traits is
necessary to understand many basic blood banking
concepts. Further insight into the various blood group
systems is presented with the discussion of each sys-
tem. The interested reader is referred to the references
for further reading.

Review Questions
1. The normal human cell contains ____ pairs of 7. Alternate forms of a gene that can occur at a single
chromosomes. chromosome locus are referred to as
a. 12 a. traits
b. 23 b. alleles
c. 46 c. chromosomes
d. 92 d. phenotypes
2. A gamete would contain ____ chromosomes. 8. Which of the following describes the expression of most
a. 23 pairs of blood group genes?
b. 46 pairs of a. dominant
c. 23 b. recessive
d. none of the above c. codominant
3. Eggs and sperm are formed through the process of d. corecessive
a. mitosis 9. For a trait to be useful as a genetic marker, which of the
b. meiosis following is important?
c. linkage a. a simple and unequivocal pattern of inheritance
d. crossing-over b. lack of polymorphism
4. With which of the following would an anti-K showing c. regular interaction with other genes that alter its
dosage react most strongly? expression
a. a red cell of the genotype Kk d. none of the above
b. a red cell of the genotype kk 10. A gene found only in a few individuals, usually in a par-
c. a red cell of the genotype KK ticular race or family, is referred to as:
d. none of the above a. an amorphic gene
5. If the frequency of gene Y is 0.4 and the frequency of b. a public gene
gene Z is 0.5, one would expect they should occur c. a private gene
together 0.2 (20%) of the time. In actuality, they are d. a genetic aberration
found together 32% of the time. This is an example of 11. True or false? A standard nomenclature used uniformly
a. crossing-over for all blood group systems exists.
b. linkage disequilibrium 12. True or false? An individual who is group A cannot
c. polymorphism product a child who is group B.
d. linkage equilibrium 13. True or false? Genes located far apart on the chromo-
6. A gene that produces no detectable product is referred some are more likely to cross over, resulting in changed
to as genetic information.
a. an amorph 14. True or false? In a direct exclusion, the child has failed
b. a trait to inherit a gene that should have been passed by the
c. an allele alleged father.
d. a polymorph 15. True or false? Some genes can inhibit the expression of
other genes.
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52 UNIT 2 Genetic and Immunologic Principles

REFERENCES ADDITIONAL READINGS

1. Campbell N, Reece J. Biology. 7th ed. San Francisco:
Benjamin-Cummings Publishing Company; 2004.
2. Brecher ME, ed. AABB Technical Manual. 15th ed.
Bethesda, MD: AABB; 2005.
3. Issit PD, Crookston MC. Blood group terminology: cur-
rent conventions. Transfusion. 1984; 24: 2.
Burns G. The Science of Genetics: An Introduction to Heredity.
2nd ed. New York: Macmillan; 1972.
Issit PD. Applied Blood Group Serology. 3rd ed. Miami:
Montgomery Scientific Publications; 1985.
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CHAPTER

5
BASIC IMMUNOLOGIC
PRINCIPLES
EVA D. QUINLEY

OBJECTIVES Hypervariable Nonspecific inflammation

Idiotype Perforin
After completion of this chapter, the reader will be able to: IgG, IgM, IgA, IgD, and IgE Phagocytosis
1. Describe cellular and humoral immunity, including clonal Immunization Plasma cell
selection theory. Immunogen Primary immune response
2. Describe the constituent cells of the immune system and Immunoglobulin Properdin pathway
their functions. Killer cell Recognition
3. Describe the interrelationship between inflammation and Leukocyte Secondary immune response
specific acquired immunity.
Light chains Self
4. Discuss the distinctive properties of antigens.
Lymphocyte Specific, acquired immunity
5. Describe structure and functions of each immunoglobulin
type. Macrophage T lymphocyte
6. Describe an antigen-antibody reaction. Memory cell Variable and constant regions
7. Explain the complement activation cascade in the classic Nonself Zeta potential
and alternate pathways.

KEY WORDS
Activation
Alternate pathway
Anamnestic response
Anaphylatoxin
Antibody
Antigen
Antigen presentation
B lymphocyte
Cell-mediated immunity
Cell surface receptors
Classic pathway
Clonal selection theory
Clone T he term “immune” is derived from the Latin
word immunis, which meant “exempt from
charges” (i.e., taxes or expenses). Today, of course, im-
Complement
munity refers to the body’s ability to resist infection
Cytokines by pathogenic microorganisms.
Cytotoxic T lymphocyte Much of what is known about immune function in
Disulfide bonds humans and the function of cells in the immune sys-
Epitope tem comes from concepts presented by Metchnikoff
and Ehrlich. Metchnikoff was a brilliant Russian biolo-
Fc receptor gist who in 1880 first described phagocytosis and
Haptens cellular immunity as he studied the role of motile cells
Heavy chains in starfish larvae that surrounded and engulfed a rose
T-helper cell thorn.1 Metchnikoff proposed correctly that inflamma-
tion included enzymatic digestion of intruders en-
Hinge region gulfed by motile cells capable of moving into tissues in
Humoral immunity a process he termed “diapedesis.”

53
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54 UNIT 2 Genetic and Immunologic Principles
In the early 1900s, Ehrlich stated his side-chain
theory that represented an attempt to explain the for-
mation of antibodies in the blood.2 It was Ehrlich’s
idea that cells in the blood had “side chains” or spe-
cific receptors on their surfaces. Once the side chain
on a cell was bound by a foreign substance, the cell
produced more side chains, which entered the blood
as antibodies.
It is a safe assumption that Metchnikoff and Ehrlich
were familiar with the foundation that had been laid a
century earlier by the English physician Jenner, who
had performed and published on the first immunization
procedures. He called these procedures “vaccination”
from the Latin vacca, meaning “cow,” because he
injected his volunteers with cowpox as a way to immu-
nize against smallpox.
Since these pioneering discoveries, an immense
and diverse body of information has been developed
in the area of biology we now call immunology. It
will be necessary to condense, simplify, and restrict
this chapter to the fundamentals of immunology that
are essential for the immunohematologist. These
areas of knowledge include cellular and humoral im-
munity, cells of the immune system and their devel-
opment, structure and function of antigens and
antibodies and their serologic behavior, the mecha-
nisms of antigen reactions and agglutination, and the
role of complement.
CELLULAR AND HUMORAL IMMUNITY
The immune system has evolved to allow recovery from
infectious disease and to provide the host organism pro-
tection from infection. This system, made up of the
leukocytes (also known as the white blood cells) and
various organs like the spleen, lymph nodes, lymphatic
channels, and the thymus, relies on complex interac-
tions between cells located in the blood, the lymph, and
in body tissues. The spleen and lymph nodes of the
immune system are composed of a lattice or meshwork
of tissue. When leukocytes travel through these organs,
the cells are trapped by the lattice formation, and effec-
tive cell–cell interaction can occur. These interactions
may lead to the production of antibodies or activated
cells capable of destroying pathogens, virus-infected
cells, or cancer cells.
The first step in launching a protective immune
response is the recognition that something foreign has
invaded the body. The immune system must be able to
distinguish self from nonself, and it relies on the
leukocytes to do so. Under certain circumstances, the
foreign, nonself substance that leads to an immune
response is known as “antigen,” abbreviated Ag. In
humans, the ability to distinguish self from nonself is
developed during embryonic growth, although how
the recognition occurs is not completely understood.
Once immune competence is established (usually by
4 to 6 months after birth in the human), external sub-
stances encountered in the body by leukocytes will be
regarded as nonself, and an immune response may be
triggered. In the period before immune competence is
established, the immune system is immature and
relatively unresponsive to antigens.
The response to antigenic challenge can be catego-
rized into two types based upon the primary actor in
the response: humoral immunity and cell-mediated
immunity. Humoral immunity may be defined as an
immune response that leads to the production of anti-
body. Cell-mediated immunity is conferred by acti-
vated leukocytes known as T lymphocytes, as well as
another class of lymphocytes called killer cells. Most
immune responses to pathogenic microorganisms in-
clude both a humoral and a cell-mediated component.
Looked at another way, most immune responses
include a nonspecific inflammatory arm as well as an
arm that includes specific, acquired immunity. When
we speak of specific, acquired immunity, we are refer-
ring to an immune response that includes antigens
binding to antibodies or structures on the surface of
lymphocytes very specifically, with a lock-and-key
type of fit. Inflammation, generated by macrophages
and neutrophils, does not require this sort of specific
binding to destroy microorganisms. These distinc-
tions cannot be fully appreciated without some
knowledge of the cells involved in the immune sys-
tem and their function.
LEUKOCYTES: CELLS OF THE
IMMUNE SYSTEM
All cellular elements of blood (red cells, leukocytes,
and platelets) derive from a pluripotent stem cell,
including those that are relevant to immune
responses. During early fetal development, these stem
cells migrate from the embryonic yolk sac into the fetal
liver, spleen, and bone marrow. It is in these sites
that the lymphoid stem cells that will eventually
produce the specific cells of the immune system, the
lymphocytes, undergo additional differentiation.
Some of these cells migrate to and mature in the
thymus and are referred to as thymus derived, or
T lymphocytes. T lymphocytes manifest cellular im-
munity but also play a “helper” role in humoral
immunity.
Other lymphoid stem cells influenced by the fetal
liver, bone marrow, or gut-associated lymphoid tissue
(GALT) differentiate to become B lymphocytes or
bone marrow–derived cells. The B lymphocytes
82043_ch05.qxd 11/11/09 5:51 PM Page 55
mature during immune responses and become the
antibody-producing plasma cells.
The immune response also involves three other
types of immunocompetent cells: macrophages,
K cells (killer cells), and natural killer (NK) cells. Some
authors group K and NK cells into a single category,
killer cells.
Macrophages
The macrophages, neutrophils, and mast cells make up
the inflammatory arm of the immune response. The
macrophage is a mononuclear cell with a nonlobulated
nucleus that may be found fixed in tissues (sessile), or
motile. Motile macrophages are mature forms of the
peripheral blood monocytes. The fixed tissue
macrophages include the Kupffer cells in the liver,
connective tissue histiocytes, and other fixed cells that
make up the so-called reticuloendothelial system.
Macrophages may also be found in the lining of sinusoid
tissues of the spleen, lymph nodes, and bone marrow.
Functionally, the macrophage is a nonspecific, phago-
cytic cell. The phagocytic macrophages engulf and de-
stroy their targets, attracted to particles in the body
when these particles are “opsonized” (i.e., coated with
either antibody or activated complement). The
macrophages find antibody- or complement-coated
particles very palatable because the macrophages have
nonspecific cell surface receptors for antibody that has
bound to its antigen. This receptor is called the Fc recep-
tor. Macrophages also have a receptor for activated
complement on their surface. The engulfment of parti-
cles like bacteria is performed when the macrophage
1. Macrophage drawn to infection site by
chemotaxis. Pseudopodia.
3. Endocytosis. Ingestion. Vacuolization.
FIGURE 5-1 Phagocytosis and antigen presentation.
CHAPTER 5 Basic Immunologic Principles 55
extends some of its cell contents to surround the parti-
cle. The cell extensions are called “pseudopodia,”
meaning “false feet.” These cells, as well as other cells of
the immune system, are drawn to the site of infection by
inflammatory chemicals called “chemotaxins.”
Macrophages do not bind their targets specifically.
In other words, the macrophage does not care if it is
engulfing a virus or a fungal particle or a sliver of wood.
In fact, it is able to phagocytize all three at once!
In addition to removing particles, pathogens,
damaged white and red blood cells (RBCs), and for-
eign organic matter from the blood, the macrophages
also serve to “process” antigens and “present” the pro-
cessed antigen to T and B cells. Once the macrophage
phagocytoses an antibody or complement-coated par-
ticle, it uses proteolytic enzymes located inside the cell
to kill and then degrade the engulfed particle into
fragments. The degraded proteins or polysaccharides
derived from the engulfed particle are displayed on
the macrophage surface in combination with a self-
protein called human leukocyte antigen (HLA) class
II, in the process called antigen presentation. The T
lymphocytes of the specific, acquired side of immu-
nity now try to bind the displayed fragment in their
specific (lock-and-key type) cell surface receptor. If the
T lymphocyte receives a specific antigen in its recep-
tor, and receives a chemical signal from the macrophage,
or if it interacts with the appropriate molecule on the
surface of the macrophage, it becomes activated and
begins generating specific, acquired immunity. These
steps are shown in Figures 5-1 and 5-2.
In addition to this primary function, many other
functions of macrophage have been identified, among
Fc receptors
Macrophage
C3 receptor
2. Attachment of Ab or C opsonized bacteria to
Fc receptors. C3 receptors on macrophage
pseudopod.
4. Granule release. Killing. Digestion to peptides.
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56 UNIT 2 Genetic and Immunologic Principles
5. HLA Class II made in the ER moves to
Golgi. Bacterial peptides move to Golgi.
Combination made.
FIGURE 5-2 Phagocytosis and antigen presentation, continued.
them is the ability to produce and secrete enzymes
that activate plasminogen, denature collagen, and
produce complement components.
Lymphocytes and Specific Antigen Binding
by Cell Surface Receptors
The B and T lymphocytes have cell surface receptors
capable of specifically binding a single antigen. It is the
physical shape of these cell surface receptor proteins
that allows the binding of one antigen and not an-
other. Think of it this way: if you hold your hands in
such a way that an orange fits snugly between them,
the shape that your hands form will not hold onto a
banana very tightly. A different shape is required to
hold the banana, and that shape will not hold the
orange. This is an example of specific binding. Of
course, the lymphocyte cell surface receptors and an-
tibodies do not need to bind oranges or bananas, but
staphylococcal bacteria, cytomegalovirus, and the
like. The cell surface receptor that binds the staphylo-
coccus does not fit tightly with the virus, and vice
versa. All of the cell surface receptors on a single lym-
phocyte, and all of the antibodies made by a single
plasma cell have the same shape. Thus, all of the cell
surface receptors on a single lymphocyte bind to only
one antigen.
T Lymphocytes
The thymic-derived lymphocytes originate in the bone
marrow and are believed to migrate early in embryonic
gIF
IL-1
6. Ag presentation to the specific T-helper cell
Ag receptor. Cytokines exchanged. Specific
immune response is launched.
life to the thymus, where they mature under the influ-
ence of thymosin and other thymic hormones. Later
they move through the lymphatic system and blood-
stream to reside in the lymph nodes and spleen. Some
remain in the bloodstream. T lymphocytes are mor-
phologically indistinguishable from B lymphocytes in
preparations made with Wright stain. To characterize
the T cells, supravital techniques or mitogen stimula-
tion is required.
T cells comprise 70% to 80% of the peripheral
blood lymphocyte population and are durable; they
have an average half-life of more than 2 years, and
some survive as long as 20 years. Functionally, the T
cell is important in providing protection against infec-
tions by viruses, fungi, and, particularly, facultative
microorganisms. A number of subpopulations or sub-
sets in the T-lymphocyte population have now been
recognized.
T-Helper Lymphocytes
T-helper cells account for approximately 40% to 60% of
the peripheral blood T-lymphocyte population. The
T-helper cell may be distinguished from other cells
of the immune system because they carry a protein on
their surface called CD4. The CD4 protein assists the
T-helper cell bind its specific surface antigen receptor to
antigen being presented by a macrophage, as shown in
Figure 5-3. The T-cell receptor is made up of two pro-
tein chains, and the presented antigen fits in the groove
between these two chains. Once the T-helper cell has
bound its specific antigen and received a signal from
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CHAPTER 5 Basic Immunologic Principles 57

HLA Class II CD4

Ag CD4+
APC T cell
TcR

CD3

Adhesion molecules,
CD28-B7 interaction

IL-1

Gamma interferon
FIGURE 5-3 CD4 + T-cell activation: launching the immune response. (Source: Garratty G, ed. Red Cell Antigens
and Antibodies. Arlington, VA: American Association of Blood Banks; 1986.)

the macrophage, it amplifies the immune response by
producing proinflammatory proteins called cytokines
that act as growth factors and help to activate other
immune system cells, as shown in Figure 5-4. It is
through the production of a mixture of cytokines that
CD4-positive T-helper cells help to activate B cells.
If a B cell has recognized its specific antigen using its
specific cell surface antigen receptor (which for the
B cell is actually antibody molecules) and has received
a cytokine signal from the T-helper cell, it divides and
differentiates to become a plasma cell, which gushes
antibody for 3 to 4 days. The antibody produced by
the plasma cell has the same antigen-binding speci-
ficity as the cell surface antigen receptor.

II-2

1. Ag presentation. TeR binding. gIF. IL-1 2. T-helper cell makes IL-2 which binds the
released. T-helper cell triggered. T cell’s IL-2 receptor. Autocrine reaction.
The T-helper cell goes on to produce
copious amounts of IL-2.

3. IL-2 + other More helper Ts

cytokines + Ag
Division of CTLs
presentation to
each cell
B cells to plasma cells.
Ab cells made.

FIGURE 5-4 CD4 + T-cell activation; launching the immune response. (Source: Garratty G, ed. Red Cell Antigens
and Antibodies. Arlington, VA: American Association of Blood Banks; 1986.)
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58 UNIT 2 Genetic and Immunologic Principles
Infectious
agent. Ag.
# Cells/[Ab]
Primary response
IgM
5-7 day lag period
FIGURE 5-5 Specific immunization and memory.
T-helper cells also play a role in the cell-mediated
immune response and participate in the graft-versus-
host reaction. The T-helper cell’s CD4 surface protein
is the site on the cell to which the human immuno-
deficiency virus attaches.
The first time a T-helper cell interacts with its
antigen, its response is relatively slow. This primary
immune response may take 5 to 7 days to generate anti-
bodies and appreciable numbers of activated cells. That
is why we often become ill during our first exposure to
a pathogen; the microorganisms have about a week to
grow in our bodies before an immune response can
destroy them. The immune response we generate to our
first exposure to a disease may allow us to recover, but
it usually will not prevent infection. However, as part of
the primary immune response, our immune systems
generate memory cells, which may circulate in our
blood for years. If we are reexposed to a pathogen to
which we have generated memory cells in the past,
these cells become activated very quickly. There is very
little lag between exposure and immunity. These sec-
ondary immune responses may actually prevent dis-
ease, and this concept is the basis of immunization or
vaccination (Fig. 5-5). All of the lymphocyte popula-
tions can generate “memory,” but the nonspecific in-
flammatory cells, like the macrophages or neutrophils,
do not.
Cytotoxic Suppressor T Cells
A second subpopulation of T lymphocytes bears a
surface protein called CD8. The CD8-positive T-cell
population is capable of carrying out two vastly
different functions. These cells can downregulate
immune responses through their suppressor function
and can also kill virus-infected cells, tumor cells, or
transplanted tissue through their cytotoxic capacities.
The CD8 cytotoxic suppressor T cells, like the CD4-
The same
infectious
agent. Ag.
Secondary
“memory”
IgG response
All IgG
No lag
Time after exposure
positive helper population, carry antigen-specific cell
surface receptors. The CD8 cells become activated
when their antigen receptor binds specifically to a tar-
get, and the cell also receives a cytokine signal from
the T-helper cell. Once activated, the cytotoxic T lym-
phocytes (CTLs) kill virus-infected cells when their
antigen receptor binds specifically to viral antigen on
the surface of the infected cell. The CD8 protein stabi-
lizes the interaction of the antigen receptor and the
viral antigen by recognizing HLA class I molecules on
the infected cell surface. Cytokines help turn on the
CTL, which activates granules in the cytoplasm that
contain a protein called perforin. Perforin kills virus-
infected cells by establishing nonspecific calcium
channels in the target cell. The rapid, uncontrolled in-
flux of calcium into the virus-infected cell poisons it,
preventing further virus replication. These steps
are displayed in Figures 5-6 and 5-7. The cytotoxic
suppressor T cells produce memory as part of the pri-
mary immune response.
Killer Cells
Killer cells are large, granular lymphocytes that
appear to have the ability to destroy tumor cells. The
nature of the antigen receptor on these cells is not
well characterized, although it is known that K
cells have Fc receptors on their surfaces. Thus, the
K cell may be drawn to an antibody-coated tumor cell
target, just as a macrophage is drawn to antibody-
coated particles.
Natural Killer Cells
The NK cells are thought to have widespread
cytotoxic ability against a variety of virally infected
and tumor cells. Their antigen receptor and method of
killing are not well understood (Fig. 5-8).